Gettin' down with ubiquitin: turning off cell-surface receptors, transporters and channels

G-protein-coupled receptors and transporters in Saccharomyces cerevisiae ar e modified with ubiquitin in response to ligand binding. In most cases, the proteasome does not recognize these ubiquitinated proteins. Instead, ubiqu itination serves to trigger internalization and degradation of plasma membr ane proteins in the lysosome-like vacuole. A number of mammalian receptors and at least one ion channel undergo ubiquitination at the plasma membrane, and this modification is required for their downregulation. Some of these cell-surface proteins appear to be degraded by both the proteasome and lyso somal proteases. Recent evidence indicates that other proteins required for receptor internalization might also be regulated by ubiquitination, sugges ting that ubiquitin plays diverse roles in regulating plasma membrane prote in activity.